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We examined two alternative models of potential functional relationships between genes in these datasets: direct convergence, in which CHD risk factors significantly and directly impact the same genes and molecules and functional convergence, in which risk factors significantly impact different molecules that participate in a discrete heart development network. We observed no evidence for direct convergence. In contrast, we show that CHD risk factors functionally converge in protein networks driving the development of specific anatomical structures (e.g., outflow tract, ventricular septum, and atrial septum) that are malformed by CHD. This integrative analysis of CHD risk factors and responses suggests a complex pattern of functional interactions between genomic variation and environmental exposures that modulate critical biological systems during heart development.<\/jats:p>","DOI":"10.1073\/pnas.1210730109","type":"journal-article","created":{"date-parts":[[2012,8,17]],"date-time":"2012-08-17T01:02:49Z","timestamp":1345165369000},"page":"14035-14040","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":125,"title":["Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development"],"prefix":"10.1073","volume":"109","author":[{"given":"Kasper","family":"Lage","sequence":"first","affiliation":[{"name":"Pediatric Surgical Research Laboratories,"},{"name":"Departments of bSurgery,"},{"name":"Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142;"},{"name":"Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800 Lyngby, Denmark;"},{"name":"Faculty of Health Sciences, Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Greenway","sequence":"additional","affiliation":[{"name":"Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA 99207;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Wakimoto","sequence":"additional","affiliation":[{"name":"Genetics, and"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Gorham","sequence":"additional","affiliation":[{"name":"Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayellet V.","family":"Segr\u00e8","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142;"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, and"},{"name":"Partners HealthCare Center for Genetics and Genomics, Boston, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B.","family":"Smoot","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, and"},{"name":"Harvard Stem Cell Institute, Boston, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"C. 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